The present invention relates to a novel DNA which is obtained from a coryneform bacterium and which regulates expression of a structural gene and to a process for efficiently producing a useful protein using the DNA. "Coryneform bacteria" hereinafter refers to microorganisms belonging to the genus Corynebacterium, Brevibacterium or Microbacterium.
Development of recombinant DNA technology has enabled utilization of various microorganisms for the production of useful polypeptides which are products of heterologous organisms. However, when a genetic product of a foreign gene is toxic to a host, expression of the foreign gene from the beginning of growth of the host causes death or growth inhibition of the host. Therefore, it is difficult to produce the genetic product in large quantities. To overcome such problem, it has been necessary to employ an expression system for inducing the expression of the foreign gene after the growth phase of a host microorganism. In E. coli which is most frequently used as a host, the expression systems for genes utilizing promoters working in response to a specific compound or under specific physical conditions have been established [Goeddel, D. , et al., Proc. Natl. Acad. Sci. U.S.A., 76, 106 (1979) , Edman, J. C., et al., Nature, 291, 503 (1981), Shimatake, H., et al., Nature, 292, 128 (1981)]. By use of these systems, a variety of useful proteins have been produced.
On the other hand, recombinant DNA technology is also applicable to coryneform bacteria which are used for production of various amino acids, purine nucleotides, and the like by fermentation. For example, a promoter for coryneform bacteria for structurally expressing a reporter gene has been obtained using a vector for detecting a promoter functioning in such bacteria (EP-A-271838). However, there are no reports of the successful development of a promoter for regulating expression in coryneform bacteria. On the other hand, a method for artificially regulating expression of a foreign gene in a coryneform bacterium using the aforesaid promoter for E. coli capable of inducing expression of a foreign gene in E. coli to induce the expression of the chloramphenicol acetyltransferase gene in coryneform bacterium has been reported (EP-B-215388). However, this method for expression is not sufficiently potent and the yield of the genetic product accumulated is small as compared with the yield obtained by using E. coli as the host.
Accordingly, in order to efficiently produce useful genetic products in coryneform bacteria, it is necessary to develop a DNA which functions in such host bacteria and which enables artificial regulation of expression of a structural gene.